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Molecular Human Reproduction, Vol. 7, No. 11, 1065-1072, November 2001
© 2001 European Society of Human Reproduction and Embryology

Uterine physiology

Induction of manganese superoxide dismutase by tumour necrosis factor-{alpha} in human endometrial stromal cells

Ayako Karube-Harada, Norihiro Sugino,1, Shiro Kashida, Shuji Takiguchi, Hisako Takayama, Yoshiaki Yamagata, Yasuhiko Nakamura and Hiroshi Kato

Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan

Abstract

The present study was undertaken to investigate the effect of tumour necrosis factor-{alpha} (TNF{alpha}) on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC) and to determine whether there is a difference in responsiveness to TNF{alpha} between ESC and decidualized ESC. TNF{alpha} increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNF{alpha} required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNF{alpha} had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either type of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibitor, blocked TNF{alpha}-induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kinase C (PKC), also inhibited TNF{alpha}-stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNF{alpha}-induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dependent phosphorylation and that de-novo protein synthesis is not required for the TNF{alpha} effect. In summary, TNF{alpha} induces Mn-SOD expression in human ESC. This phenomenon may be important for protection of ESC from cytokine-mediated oxidative stress.

endometrial stromal cells/protein kinase C/superoxide dismutase/superoxide radical/TNF{alpha}

Notes

1 To whom correspondence should be addressed. E-mail: obgyn{at}po.cc.yamaguchi-u.ac.jp


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